Various cell mechanisms are regulated by ligand dependent transcriptional factors. The regulation by the ligand dependent transcriptional factors is usually achieved because the ligand dependent transcriptional factor has an activity for transactivation of a gene. It has been postulated that in transactivation, the ligand dependent transcription factor and a RNA polymerase II complex interact together at a gene to increase the rate of gene expression. The transactivation can often determine in eukaryotic cells, whether a gene is sufficiently expressed to regulate the various cell mechanisms.
Such transactivation by the ligand dependent transcriptional factors can occur when the ligand dependent tranactivational factor is selectively bound to its cognate ligand and to its cognate responsive element sequence. In this regard, the presence of the cognate responsive element in a gene or the presence of its cognate ligand in the cell can determine whether the ligand dependent transcriptional factor can transactivate the gene.
ERα is an example of such ligand dependent transcriptional factors. ERα is naturally found in the target cells of estrogen such as in ovary cells, breast cells, uterus cells, bone cells and the like. The transactivation activity of ERα typically occurs when ERα is selectively bound to an ERE and an estrogen such as E2. It is reported that aberrant transactivation by ERα may contribute to various disorders. Attempts have been made to use anti-estrogens that are antagonistic to a normal ERα. Examples of such anti-estrogens used with such disorders include tamoxifen, raloxifene, 4-hydroxytamoxifen and the like.